A Study of TAK-019 in Healthy Japanese Adults (COVID-19)

• ClinicalTrials.gov Identifier: NCT04712110
• Recruitment Status: Completed
• First Posted: January 15, 2021
• Last Update Posted: April 14, 2022
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

TAK-019 is a vaccine in development to protect people against Covid-19. The main aims of the study are to learn if TAK-019 can protect people from Covid-19 and to check for side effects from TAK-019.

At the first visit, the study doctor will check if each person can take part. Those who can take part will be chosen for 1 of 2 treatments by chance. Participants will either receive an injection of TAK-019 or a placebo in their arm. In this study, a placebo will look like the TAK-019 vaccine but will not have any medicine in it. 3 times as many participants will receive TAK-019 than placebo. Participants will receive 2 injections of TAK-019 or placebo, 21 days apart.

Participants will be asked to record their temperature and any medical problems in an electronic diary for up to 7 days after each injection.

During the study, participants will visit the clinic for regular check-ups, blood tests, and sometimes for nose swab samples. When all participants have attended a clinic visit 28 days after their 2nd injection, the study sponsor (Takeda) will check how many participants have made enough antibodies to protect them against Covid-19.

The participants will stay in the study for up to 12 months after they have had their 2nd injection. During this time, the study doctors will continue to check how many participants have made enough antibodies to protect them against Covid-19. Also, they will check if participants have any more side effects from TAK-019 or the placebo.

Condition or disease	Intervention/treatment	Phase
Prevention of Infection Disease Caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)	Biological: TAK-019; Biological: Placebo	Phase 1; Phase 2

Detailed Description:

The drug being tested in this study is called TAK-019. TAK-019 is being tested to prevent infectious disease caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2). This study will look at the evaluate the safety and immunogenicity of 2 doses of TAK-019 by intramuscular (IM) injection 21 days apart in healthy Japanese male and female adults.

The study will enroll approximately 200 healthy volunteers. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• TAK-019 0.5 mL
• Placebo- this is an injection that looks like the study drug but has no active ingredient

All participants will be asked to take intramuscular injection in the upper arm twice throughout the study.

This multi-center trial will be conducted in Japan. The overall time to participate in this study is 12 months from the second vaccination (totally 387 days). Participants will make multiple visits to the clinic and will be contacted by telephone or a final visit after the last vaccination for a follow-up assessment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 1/2, Randomized, Observer-Blind, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of TAK-019 by Intramuscular Injection in Healthy Japanese Male and Female Adults Aged 20 Years and Older (COVID-19)
• Actual Study Start Date: February 24, 2021
• Actual Primary Completion Date: March 29, 2022
• Actual Study Completion Date: March 29, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: TAK-019; TAK-019 0.5 mL, intramuscular injection in the upper arm	Biological: TAK-019; TAK-019 intramuscular injection
Placebo Comparator: Placebo; TAK-019 Matching Placebo, intramuscular injection in the upper arm	Biological: Placebo; Placebo intramuscular injection

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants with Reported Solicited Local Adverse Events (AEs) for 7 Days Following Each Vaccination [ Time Frame: 7 days after each vaccination ]
   An AE is defined as any untoward medical occurrence in a clinical investigation subject administered an investigational medicinal product (IMP); it does not necessarily have to have a causal relationship with IMP administration. Reported solicited local AEs are defined as injection site pain, tenderness, erythema/redness, induration, and swelling.
2. Percentage of Participants with Solicited Systemic AEs for 7 Days Following Each Vaccination [ Time Frame: 7 days after each vaccination ]
   Solicited systemic AEs are defined as fever, fatigue, malaise, myalgia, arthralgia, nausea/vomiting, and headache.
3. Percentage of Participants with Unsolicited AEs for 49 Days Following First Vaccination (Day 1) [ Time Frame: 49 days after first vaccination (Day 1) ]
   Unsolicited AEs defines as other AEs than solicited local AEs and solicited systemic AEs.
4. Percentage of Participants with Serious Adverse Events (SAE) until Day 50 [ Time Frame: Up to Day 50 ]
   An SAE is defined as any untoward medical occurrence that: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Leads to a congenital anomaly/birth defect in the offspring of a participant, or Is an important medical event.
5. Percentage of Participants with Adverse Event of Special Interest (AESI) until Day 50 [ Time Frame: Up to Day 50 ]
   An AESI is defined as AEs that will be specifically highlighted to the Investigator. AESIs for the study include the Potential Immune Mediated Medical Conditions (PIMMC) and AEs specific to COVID-19. PIMMC is categorized as following; Neuroinflammatory Disorders, Musculoskeletal and Connective Tissue Disorders, Vasculitides, Gastrointestinal Disorders, Hepatic Disorders, Renal Disorders, Cardiac Disorders, Skin Disorder, Hematologic Disorders, Metabolic Disorders, and Other Disorders.
6. Percentage of Participants with Medically-Attended Adverse Events (MAAEs) until Day 50 [ Time Frame: Up to Day 50 ]
7. Percentage of Participants with Any AE Leading to Discontinuation of Vaccination [ Time Frame: Up to Day 50 (up to discontinuation of vaccination) ]
8. Percentage of Participants with Any AE Leading to Participant's Withdrawal from the Trial until Day 50 [ Time Frame: Up to Day 50 ]
9. Percentage of Participants with SARS-CoV-2 Infection until Day 50 [ Time Frame: Up to Day 50 ]
10. Geometric Mean Titers (GMT) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 36 [ Time Frame: Day 36 ]
11. Geometric Mean Fold Rise (GMFR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 36 [ Time Frame: Day 36 ]
12. Seroconversion Rate (SCR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 36 [ Time Frame: Day 36 ]
    SCR is defined at proportion of participants with 4-fold or more rises in titer if naive at baseline OR proportion of participants with 2-fold or more rises in titer if seropositive at baseline.
13. Seroresponce Rate (SRR) of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 36 [ Time Frame: Day 36 ]
    SRR is defined at proportion of participants with 95 percentile or more in titer at baseline (Day 1) for all participants.

Secondary Outcome Measures :

1. Percentage of Participants with SAE throughout the Trial [ Time Frame: Up to Day 387 ]
2. Percentage of Participants with AESI throughout the Trial [ Time Frame: Up to Day 387 ]
3. Percentage of Participants with MAAEs throughout the Trial [ Time Frame: Up to Day 387 ]
4. Percentage of Participants with Any AE Leading to Participant's Withdrawal from the Trial from the Day of Vaccination throughout the Trial [ Time Frame: Up to Day 387 ]
5. Percentage of Participants with SARS-CoV-2 Infection throughout the Trial [ Time Frame: Up to Day 387 ]
6. GMT of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 22, 50, 202, and 387 [ Time Frame: Day 22, 50, 202, and 387 ]
7. GMFR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 22, 50, 202, and 387 [ Time Frame: Day 22, 50, 202, and 387 ]
8. SCR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 22, 50, 202, and 387 [ Time Frame: Day 22, 50, 202, and 387 ]
   SCR is defined at proportion of participants with 4-fold or more rises in titer if naive at baseline OR proportion of participants with 2-fold or more rises in titer if seropositive at baseline.
9. SRR of Serum IgG Antibody Levels to SARS-CoV-2 rS Protein on Day 22, 50, 202, and 387 [ Time Frame: Day 22, 50, 202, and 387 ]
   SRR is defined at proportion of participants with 95 percentile or more in titer at baseline (Day 1) for all participants.
10. GMT of Serum Neutralizing Antibody Titters to Wild-type Virus on Day 22, 36, 50, 202, and 387 [ Time Frame: Day 22, 36, 50, 202, and 387 ]
11. GMFR of Serum Neutralizing Antibody Titters to Wild-type Virus on Day 22, 36, 50, 202, and 387 [ Time Frame: Day 22, 36, 50, 202, and 387 ]
12. SCR of Serum Neutralizing Antibody Titters to Wild-type Virus on Day 22, 36, 50, 202, and 387 [ Time Frame: Day 22, 36, 50, 202, and 387 ]
    SCR is defined at proportion of participants with 4-fold or more rises in titer if naive at baseline OR proportion of participants with 2-fold or more rises in titer if seropositive at baseline.
13. SRR of Serum Neutralizing Antibody Titters to Wild-type Virus on Day 22, 36, 50, 202, and 387 [ Time Frame: Day 22, 36, 50, 202, and 387 ]
    SRR is defined at proportion of participants with 95 percentile or more in titer at baseline (Day 1) for all participants.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Healthy Japanese male and female adult participants aged >= 20 years of age at the time of signing of informed consent.
2. Participants who understand and are willing to comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

1. Participants who received any other SARS-CoV-2 or other experimental novel coronavirus vaccine prior to the trial.
2. Participants who have close contact of anyone known to have COVID-19 within 30 days prior to the trial vaccination.
3. Participants who were tested positive for SARS-CoV-2 prior to the trial or before the trial vaccination.
4. Participants who are on current treatment with other investigational agents for prophylaxis of COVID-19.
5. Participants who have traveled outside of Japan in the 30 days prior to the trial participation.
6. Participants with a clinically significant active infection (as assessed by the Investigator) or oral temperature >= 38 degree Celsius within 3 days of the intended date of vaccination.
7. Participants with known hypersensitivity or allergy to any of the investigational vaccine components.
8. Participants with history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial.
9. Participants with known or suspected impairment/alteration of immune function, including history of any autoimmune disease or neuro-inflammatory disease.
10. Abnormalities of splenic or thymic function.
11. Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
12. Participants with any serious chronic or progressive disease (eg, neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
13. Participants with body mass index (BMI) greater than or equal to 30 kg/m^2 (BMI= weight in kg/ height in meters^2).
14. Participants participating in any clinical trial with another investigational product within 30 days prior to the trial vaccination or intend to participate in another clinical trial at any time during the conduct of this trial.
15. Participants who received or plan to receive any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to trial dose administration.
16. Participants with acute or chronic clinically significant disease including pulmonary, cardiovascular, hepatic or renal abnormality evaluated by physical examination.
17. Participants involved in the trial conduct or their first degree relatives.
18. Participants who have history or infection of hepatitis B, hepatitis C, and human immunodeficiency virus infection.
19. Female participants who are pregnant or breastfeeding.

Contacts and Locations

Locations

Japan

Sumida Hospital

Sumida-ku, Tokyo, Japan

Nishi Kumamoto Hospital

Kumamoto, Japan

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Study Director; Takeda

More Information

Additional Information:

To obtain more information on the study, click here/on this link 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Masuda T, Murakami K, Sugiura K, Sakui S, Schuring RP, Mori M. Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial. Vaccine. 2022 May 26;40(24):3380-3388. doi: 10.1016/j.vaccine.2022.04.035. Epub 2022 Apr 29.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT04712110
• Other Study ID Numbers: TAK-019-1501; U1111-1262-6244 ( Other Identifier: WHO ); jRCT2071200084 ( Registry Identifier: jRCT )
• First Posted: January 15, 2021
• Last Update Posted: April 14, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases